This application relates, inter alia, to the field of polymer chemistry, and more particularly to reversible modification of natural polysaccharides.
One of the major challenges in the field of medicine is the rampant increase in cases of antimicrobial drug resistance. Small molecules based antimicrobials have the formation of drug resistance, which can be attributed to misuse of available antimicrobial. Almost all currently available conventional antibiotics have a microbe that has developed a resistance to that drug molecule through some mechanism of drug resistance formation.
Gene silencing has been recently shown to be possible in eukaryotic cells through the use of RNAi (micro (miRNA), double stranded (dsRNA), small interfering (siRNA), piwi (piRNA). With the recent advent of CRISPR RNA (crRNA), prokaryotic gene silencing becomes a possibility for treatment of drug resistant infections.
Antimicrobial materials have been present in the field of medicine for many years, with the most well-known being silver. Silver, as well as many other metals and metal oxides, such as gold, aluminum, zinc oxide, and titanium dioxide hinder or eliminate microbe growth either through reactive oxygen species (ROS) or physically hindering key biological processes. Furthermore there are a plethora of synthetic polymers and other nanoantibiotic material all of which destroy microbes through generation of ROS, cell membrane permeation, triggering DNA damage, or interrupting trans-membrane electron transport. The term nanoantibiotic refers to nanomaterials having antibiotic capabilities.
An added advantage of nanoantibiotics is the possibility to target intracellular infections which are usually the most difficult to target due to intracellular diffusion kinetics and lack of drug accessibility to desired locations. While a majority of these nanoantibiotic materials are very effective against microbes, some are toxic to the host cells as well and limits use. Moreover, with the focus of engineering new antimicrobial that encompasses gene silencing, a vector capable material is desired.
Chitosan is an abundant natural material that is biogradeable with no reported toxicity. Difficulties with chitosan lies in the lack of solubility in biologically relevant pH, and ineffective release. There is a need in the art for compositions and method to overcome this difficulties by improving solubility of chitosan, aiding in transfection of chitosan, and creating a process that can be applied to other polymeric nanoantibiotics. Provided herein are solutions to these and other problems in the art.